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A Quantitative LC-MS/MS Method for Determination of Liposomal Amphotericin B in Rat Plasma and Tissues, and its Application to a Toxicokinetic and Tissue Distribution Study

Author(s):

Quanyu Xu, Yueyue Qian, Yanjuan Yuan, Qing Shao, Xuejun He and Hongqun Qiao*   Pages 1 - 12 ( 12 )

Abstract:


Background: Among the existing antifungal drugs, Amphotericin B is the first drug in the treatment of systemic fungal infections. But its large adverse reactions limit the clinical application and Liposome Amphotericin B resolves the problem.

Objective: In the present study, a rapid, simple, sensitive and efficient method based on LC-MS/MS for determination of liposomal Amphotericin B in rat plasma and tissue samples using natamycin as the internal standard has been developed and validated.

Method: The analytical samples contain the plasma and various tissues disposed by protein precipitation and determination of liposomal Amphotericin B by an LC-MS/MS. Chromatographic separation was achieved on a Poroshell 120 EC-C18 column (4.6 mm × 50 mm, 2.7 μm) with 10 mmol/L ammonium acetate in water-acetonitrile by gradient elution at a flow rate of 0.7 mL/min. The MS analysis was conducted in positive electrospray ionization with the multiple reaction monitoring (MRM).

Results: The calibration curves of plasma and tissues showed good linear range from 50 to 10000 ng/mL. The analysis samples contained plasma and tissues were stable under different storage conditions and temperature.

Conclusions: The developed LC-MS/MS method has been successfully applied to the studies of toxicokinetics and tissue distribution after intravenous injection of liposomal Amphotericin B to rats.

Keywords:

liposomal Amphotericin B, LC-MS/MS, toxicokinetic, tissue distribution, rats, intravenous injection

Affiliation:

School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211816, School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211816, Jiangsu Provincial Institute Of Materia Medica, Nanjing 211816, Jiangsu Provincial Institute Of Materia Medica, Nanjing 211816, School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211816, School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211816



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